Cationic cyclodextrins chemically-bonded chiral stationary phases for high-performance liquid chromatography

Two covalently bonded cationic β-CD chiral stationary phases (CSPs) prepared by graft polymerization of 6^A-(3-vinylimidazolium)-6-deoxyperphenylcarbamate-β-cyclodextrin chloride or 6^A-(N,N-allylmethylammonium)-6-deoxyperphenylcarbamoyl-β-cyclodextrin chloride onto silica gel were successfully applied in high-performance liquid chromatography (HPLC). Their enantioseparation capability was examined with 12 racemic pharmaceuticals and 6 carboxylic acids. The results indicated that imidazolium-containing β-CD CSP afforded more favorable enantioseparations than that containing ammonium moiety under normal-phase HPLC. The cationic moiety on β-CD CSPs could form strong hydrogen bonding with analytes in normal-phase liquid chromatography (NPLC) to enhance the analytes’ retention and enantioseparations. In reversed-phase liquid chromatography (RPLC), the analytes exhibited their maximum retention when the pH of mobile phase was close to their pK_a value. Inclusion complexation with CD cavity and columbic/ionic interactions with cationic substituent on the CD rim would afford accentuated retention and enantioseparations of the analytes.     

Copolymeric cyclodextrin polysiloxane stationary phases prepared from 6A,6C- and 6A,6D-dialkenyl-substituted β-cyclodextrin

The syntheses of four new β-cyclodextrin-hexasiloxane copolymers from heptakis(2,3-di-O-methyl)-β-cyclodextrin (2) by multi-step processes are described. 6^A,6^C-Di-O-[p,p'-methylenebis(benzenesulfonyl)]hetakis(2,3-di-O-methyl)β-cyclodextrin (3) , which was prepared by the reaction of 2 with p,p'-methylenebis-(benzenesulfonyl chloride), is a key intermediate for the preparation of permethylated 6^A,6^C-bisalkenyl-β-cyclodextrins 5, 6 , and 9. Permethylated 6^A,6^C-bissulfonate ester 4 , which was obtained from 3 by a methylation reaction under mild conditions, was reacted with sodium allyloxide or sodium ω-undecenyloxide to produce permethylated 6^A,6^C-bisallyl- (or bis-ω-undecenyl)-β-cyclodextrin 5 or 6 or was hydrolyzed with 2% sodium amalgam in methanol to yield diol 7. Compound 7 was oxidized with periodinane, followed by Wittig's reaction with methyltriphenylphosphonium iodide to give permethylated 6^A,6^C-dideoxy-6^A,6^C-dimethylene-β-cyclodextrin (9). Treatment of 2 with p,p'-methylenebis(benzenesulfonyl chloride) or p,p'-biphenyldisulfonyl chloride gave bissulfonate esters 10 or 11 , respectively. Both of them were treated with sodium p-allyloxy-phenoxide in DMF, followed by methylation, to form permethylated 6^A,6^D-di-O-(p-allyloxyphenyl)-β-cyclo-dextrin (16). Bisalkenes 5, 6, 9 and 16 were copolymerized with α,ω-dioctyldecamethylhexasiloxane by a hydrosilylation process to give the cyclodextrin-containing copolymers 17–20.     

Cyclodextrin chemistry. Selective modification of all primary hydroxyl groups of α- and β-cyclodextrins

Two efficient methods are described for the selective modification of all six primary hydroxyl groups of α-cyclodextrin (α-CD, 1 1 ). One, using an indirect strategy, involves protection of all 18 hydroxyl functions as benzoate esters, followed by selective deprotection of the six primary alcohol groups. The other, using a direct strategy, involves selective activation of the primary hydroxyl groups via a bulky triphenylphosphonium salt, which is then substituted by azide anion as the reaction proceeds. A number of modified α-cyclodextrin derivatives have been prepared and fully characterized, among which are: the useful intermediate α-cyclodextrin-dodeca (2, 3) benzoate ( 3 ); hexakis (6-amino-6-deoxy)-α-cyclodextrin hexahydrochloride ( 7 ); hexakis (6-amino-6-deoxy)-dodeca (2, 3)-O-methyl-α-cyclodextrin hexahydrochloride ( 9 ), hexa (6)-O-methyl-α-cyclodextrin ( 13 ). The direct substitution is shown to be even more efficient for β-cyclodextrin ( 16 ), giving the heptakis (6-azido-6-deoxy)-β-CD-tetradeca (2, 3)acetate ( 17 ), while the indirect strategy fails. The compounds are characterized by extensive use of ¹³C- and ¹H-NMR. spectroscopy. The steric and statistical problems of selective polysubstitution reactions for the cyclodextrins are discussed, and possible reasons for the observed differences in reactivity between α- and β-cyclodextrins are examined. The dodecabenzoate 3 presents a very marked solvent effect on physical properties (IR. and NMR. spectra, optical rotation); the effects observed may be ascribed to an unusually strong intramolecular network of hydrogen bonds which severely distorts the α-cyclodextrin ring and lowers the symmetry from six-fold to three-fold.     

1H NMR Studies of Hydroxy Protons of ASN- and Ser-Linked Disaccharides in Aqueous Solution

ABSTRACT

The hydroxy protons of β-D-GlcpNAc-(1→4)-β-D-GlcpNAc, β-D-GlcpNAc-(1→4)-β-D-GlcpNAc-N-Asn, β-D-Galp-(1→3)-α-D-GalpNAc-O-Me and of β-D-Galp-(1→3)-α-D-GalpNAc-O-Ser in aqueous solution have been investigated using ¹H NMR spectroscopy. The chemical shifts, coupling constants, temperature coefficients, exchange rates and NOEs have been measured. The O(3)H proton of β-D-GlcpNAc-(1→4)-β-D-GlcpNAc and β-D-GlcpNAc-(1→4)-β-D-GlcpNAc-N-Asn, and the O(2')H proton of β-D-Galp-(1→3)-α-D-GalpNAc and β-D-Galp-(1→3)-α-D-GalpNAc-O-Ser have values which differ significantly from the other hydroxy protons. Both these hydroxy protons are shielded when compared to those of the corresponding monosaccharide methyl glycosides. This shielding is attributed to the proximity of these protons to the O(5') oxygen and to the 2-acetamido group, respectively. In β-D-GlcpNAc-(1→4)-β-D-GlcpNAc and β-D-GlcpNAc-(1→4)-β-D-GlcpNAc-N-Asn, the O(3)H proton has restricted conformational freedom with a preferred orientation towards the O(5') oxygen, and is protected from exchange with the bulk water through a weak hydrogen bond interaction with O(5'). In β-D-Galp-(1→3)-α-D-GalpNAc-O-Me and β-D-Galp-(1→3)-α-D-GalpNAc-O-Ser, the O(2')H is protected from exchange with the bulk water by the 2-acetamido group. The conformations of the disaccharides are not affected by the amino acid, and no interaction in terms of hydrogen bonding between the sugars and the amino acid residue could be observed.     

Surface-up click access to allylimidazolium bridged cyclodextrin dimer phase for efficient enantioseparation

In this work, a novel allylimidazolium-bridged bis(β-cyclodextrin) chiral stationary phase was fabricated via a surface-up thiol-ene click chemistry reaction between 7-SH-β-cyclodextrin and 1-allylimidazole-β-cyclodextrin bonded on a silica surface. The structure of the allylimidazolium-bridged bis(β-cyclodextrin) chiral stationary phase was characterized by Fourier transform infrared spectra, ¹³C nuclear magnetic resonance, thermogravimetric analysis, and elemental analysis. Its chiral chromatographic performances were systematically evaluated by separating 35 racemic analytes including isoxazolines, dansyl-amino acids, and flavanones under reversed-phase high-performance liquid chromatography. Compared with the corresponding bottom and top layer of the β-cyclodextrin stationary phase, the allylimidazolium-bridged bis(β-cyclodextrin) chiral stationary phase afforded significantly accentuated chiral recognition ability due to its abundant hydrogen bond sites, electrostatic interactions, and synergistic inclusion. Furthermore, the allylimidazolium-bridged bis(β-cyclodextrin) chiral stationary phase showed better enantioseparation ability compared to other reported bridged cyclodextrin stationary phases. In particular, Ar-Phs and dansyl-amino acid could be completely separated by allylimidazolium-bridged bis(β-mono-6^A-deoxy-6-allylimidazolium-β-cyclodextrin chiral stationary phase) chiral stationary phase with high resolutions of 1.14–7.20 and 3.16–5.82, respectively. Molecular docking reveals that good enantioseparation ability arises from the different interaction modes and the synergistic effect of allylimidazolium-bridged bis(β-cyclodextrin) chiral stationary phase.     

Dimerisation and complexation of 6-(4′-t-butylphenylamino)naphthalene-2-sulphonate by β-cyclodextrin and linked β-cyclodextrin dimers

This study shows that stereochemical factors largely determine the extent to which 6-(4′-t-butylphenylamino)-naphthalene-2-sulphonate, BNS^?  and its dimer, (BNS^? )₂, are complexed by β-cyclodextrin, βCD, and a range of linked βCD dimers. Fluorescence and ¹H NMR studies, respectively, show that BNS^?  and (BNS^? )₂ form host–guest complexes with βCD of the stoichiometry βCD.BNS^?  (10^? 4 K ₁ = 4.67 dm³ mol^? 1) and βCD.BNS₂ ^2 ?  (10^? 2 K ₂′ = 2.31 dm³ mol^? 1), where the complexation constant K ₁ = [βCD.BNS^? ]/([βCD][BNS^? ]) and K ₂′ = [βCD. (BNS^? )₂]/([βCD.BNS^? ][BNS^? ]) in aqueous phosphate buffer at pH 7.0, I = 0.10 mol dm³ at 298.2 K. (The dimerisation of BNS^?  is characterised by 10^? 2 K _d = 2.65 dm³ mol^? 1.) For N,N-bis((2^AS,3^AS)-3^A-deoxy-3^A-β-cyclodextrin)succinamide, 33βCD₂su, N-((2^AS,3^AS)-3^A-deoxy-3^A-β-cyclodextrin)-N′-(6^A-deoxy-6^A-β-cyclodextrin)urea, 36βCD₂su, N,N-bis(6^A-deoxy-6^A-β-cyclodextrin)succinamide, 66βCD₂su, N-((2^AS,3^AS)-3^A-deoxy-3^A-β-cyclodextrin)-N′-(6^A-deoxy-6^A-β-cyclodextrin)urea, 36βCD₂ur, and N,N-bis(6^A-deoxy-6^A-β-cyclodextrin)urea, 66βCD₂ur, the analogous 10^? 4 K ₁ = 11.0, 101, 330, 29.6 and 435 dm³ mol^? 1 and 10^? 2 K ₂′ = 2.56, 2.31, 2.59, 1.82 and 1.72 dm³ mol^? 1, respectively. A similar variation occurs in K ₁ derived by UV–vis methods. The factors causing the variations in K ₁ and K ₂ are discussed in conjunction with ¹H ROESY NMR and molecular modelling studies.     

Regioselective Syntheses of New Tri-and Tetrasaccharides by Transglycosylation of Trichoderma Viride β-Glucosidase

ABSTRACT

A new β-glucosidase, which was partially purified from Trichoderma viride cellulase, catalyzed a transglycosylation reaction of cellobiose to give β-D-Glcp-(1→6)-β-D-Glcp-(1→4)-D-Glcp 1 and β-D-Glcp-(1→6)-β-D-Glcp-(1→6)-β-D-Glcp-(1→4)-D-Glcp 2, regioselectively. Furthermore, the enzyme converted laminaribiose and gentiobiose into β-D-Glcp-(1→6)-β-D-Glcp-(1→3)-D-Glcp 3 and β-D-Glcp-(1→6)-β-D-Glcp-(1→6)-D-Glcp 4, respectively. Selective β-(1→6) transglycosylation was achieved.     

Chromatographic and Spectroscopic Studies on β-Cyclodextrin Functionalized Ionic Liquid as Chiral Stationary Phase: Enantioseparation of Flavonoids

In this study, β-cyclodextrin functionalized ionic liquid was prepared by adding 1-benzylimidazole onto 6-monotosyl-6-deoxy-β-cyclodextrin (β-CDOTs) to obtain β-CD-BIMOTs. β-CD-BIMOTs were then bonded onto the modified silica to produce chiral stationary phases (β-CD-BIMOTs-CSP). The performance of β-CD-BIMOTs-CSP was evaluated by observing the enantioseparation of flavonoids. The performance of β-CD-BIMOTs stationary phase was also compared with native β-CD stationary phase. For the selected flavonoids, flavanone and hesperetin obtained a high resolution factor in reverse phase mode. Meanwhile, naringenin and eriodictyol attained partial enantioseparation in polar organic mode. In order to understand the mechanism of separation, the interaction of selected flavonoids and β-CD-BIMOTs was studied using spectroscopic methods (¹H NMR, NOESY and UV–Vis spectrophotometry). The enantioseparated flavanone and hesperetin were found to form an inclusion complex with β-CD-BIMOTs. However, naringenin and eriodictyol were not enantioseparated due to the formation of hydrogen bonding at exterior torus of β-CD-BIMOTs.

     

Cyclodextrins as chiral stationary phases in capillary gas chromatography. Part II: Heptakis(3-O-acetyl-2,6-di-O-pentyl)-ß-cyclodextrin

Heptakis (3-O-acetyl-2,6-di-O-pentyl)-ß-cyclodextrin is used as a chiral stationary phase in capillary gas chromatography. High enantioselectivity towards trifluoro-acetylated α and β-chiral amines, amino alcohols, α- and β-amino acid esters, and cyclic trans-diols is observed. In contrast to chiral polysiloxane phases, where hydrogen bonding interaction is essential for enantiomer separation, in cyclodextrins inclusion properties contribute to enantioselectivity. This can be concluded from the separation of N-alkylated amino compounds. The new chiral stationary phase exhibits a wide operating temperature range and is stable above 200°C.     

Synthetic Studies on Sialoglycoconjugates 22: Total Synthesis of Tumor-Associated Ganglioside,Sialyl Lewis X1

ABSTRACT

The first total synthesis of tumor-associated glycolipid antigen, sialyl Lewis X is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (1) with methyl 2,3,4-tri-O-benzyl-1-thio-β-L-fuco-pyranoside (4) gave the α-glycoside (5), which was converted by reductive ring-opening of the benzylidene acetal into the glycosyl acceptor (6). Dimethyl(methylthio)sulfonium triflate-promoted coupling of 6 with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-D-galactopyranoside (7) afforded the desired hexasaccharide 8 in good yield. Compound 8 was converted into the α-trichloroacetimidate 11, via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile, which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octa-decene-1,3-diol (12), gave the β-glycoside 13. Finally, 13 was transformed, via selective reduction of the azide group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title compound 16.     

Convenient synthesis of mono(6-N-allylamino-6-deoxy)permethylated β-cyclodextrin: a promising chiral selector for an HPLC chiral stationary phase

Mono(6-(p-toluenesulfonyl))permethylated β-cyclodextrin, a versatile precursor for a wide variety of mono-functionalized permethyl β-cyclodextrins, has been generated successfully by the direct methylation of monotosylated cyclodextrin. This afforded a convenient synthesis of mono(6^A-N-allylamino-6^A-deoxy)permethylated β-cyclodextrin. Hydrosilylation of the chiral selector with (EtO)₃SiH and reaction of the resultant reactive siloxane with pristine silica gel afforded a facile entry into a structurally well-defined chiral HPLC stationary phase.     

Synthese und Chiralität von (5S, 6R)-5,6-Epoxy-5,6-dihydro-β,β-carotin und (5R, 6R)-5,6-Dihydro-β,β-carotin-5,6-diol,einem Carotinoid mit ungewöhnlichen Eigenschaften

Synthesis and Chirality of (5S,6R)-5,6-Epoxy-5,6-dihydro-β,β-carotene and (5R,6R)-5,6-Dihydro-β,β-carotene-5,6-diol, a Compound with Unexpected Solubility Characteristics Wittig-condensation of azafrinal ( 1e ) with the phosphorane derived from 7 leads to a (1:3)-mixture of (E)-9′- and (Z)-9′-β,β-carotene-diol 3 , from which pure and optically active 3 ((5R,6R)-5,6-dihydro-β,β-carotene-5,6-diol) has been isolated as bright violet leaflets, m.p. 168°. Due to the trans-configuration of the diol moiety and to severe steric hindrance, hydrogen bonding is reduced to such an extent, that 3 behaves much more as a hydrocarbon than as a diol. There is good evidence that the so-called ‘β-oxycarotin’ obtained by Kuhn & Brockmann [15] by chromic acid oxidation of β, β-carotene is the corresponding racemic cis-diol. 3 has been converted into (5S, 6R)-5,6-epoxy-5.6-dihydro-β,β-carotene ( 4 ), m.p. 156°. This transformation establishes for the first time the chirality of a caroteneepoxide (without other O-functions). Full spectral and chiroptical data including a complete assignement of ¹³C-chemical shifts for azafrin methyl ester and 3 are presented.     

A Cyclodextrin Molecular Reactor for the Regioselective Synthesis of 1,5-disubstituted-1,2,3-triazoles

6^A-Deoxy-6^A-propynamido-β-cyclodextrin reacts with 4-tert-butylphenyl azide in aqueous solution, to form the 5-(aminocarbonyl)-substituted triazole in preference to the 4-(aminocarbonyl)-substituted analogue, in a ratio of 25:1. The cyclodextrin moiety templates the reaction through the formation of a host-guest complex of the dipole with the dipolarophile, controlling the regioselectivity of cycloaddition. In a control reaction under similar conditions, with propiolamide instead of the cyclodextrin derivative, 5- and 4-(aminocarbonyl)-1-(4-tert-butylphenyl)-1,2,3-triazole were formed in a ratio of 1:4. As well as reversing the regioselectivity, the cyclodextrin substituent increases the rate of cycloaddition, by at least two orders of magnitude for the reaction to give the 5-substituted cycloadduct. Even the rate of formation of the 4-substituted cycloadduct is increased by a factor of two. Less marked effects are observed with phenyl azide and 4-tert-butylbenzyl azide as dipoles.     

A built-in route leading to a self-inclusion complex of 6A,6B-(bis-O-p-allyloxyphenyl)hexakis(2,3-di-O-methyl)-α-cyclodextrin

Hexakis(2,3-di-O-methyl)-α-cyclodextrin was treated with 2,4-dimethoxybenzene-1,5-disulfonyl chloride to give 6^A,6^B-di-O-sulfonated product 5 in only a 3.0% yield. When treated with sodium p-allyloxyphenoxide, 5 gave 6^A,6^B-(bis-O-p-allyloxyphenyl)hexakis(2,3-di-O-methyl)-α-cyclodextrin (6) in a 57% yield. A careful ¹H nmr analysis of 6 shows that one of the allyloxphenyl groups is in the α-cyclodextrin cavity. This is the first intramolecular complex formed from a modified α-cyclodextrin. Molecular modeling was used to explain the experimental facts. A novel built-in route leading to a self-inclusion α-cyclodextrin complex is proposed for this reaction.     

七-(2,6-二-O-甲基)-β-环糊精对1,1'-联萘酚对映体手性识别的电喷雾质谱研究

利用电喷雾质谱研究了β-环糊精、七-(2,6-二-O-甲基)-β-环糊精作为手性识别试剂对1,1'-联萘酚对映体的手性识别效应. 实验结果表明, 在气相中, β-环糊精与七-(2,6-二-O-甲基)-β-环糊精都可以与联萘酚形成非共价复合物. 对形成的复合物的串联质谱研究表明, β-环糊精不能识别联萘酚对映体, 而七-(2,6-二-O-甲基)-β-环糊精对联萘酚对映体有较强的手性识别效应. 进一步研究表明七-(2,6-二-O-甲基)-β-环糊精与联萘酚对映体混合比例以及CID能量对于手性识别并无影响.     

Preparation and characterization of phenyl carbamate derivative β-cyclodextrin bonded phase for chiral HPLC

A partially substituted β-cyclodextrin chiral stationary phase was prepared by the reaction of phenyl isocyanate. The enantiomers of a series of O,O-diethyl(p-methylbenzenesulfonamido)-aryl(or alkyl)-methylphosphonates were studied on the prepared phenyl carbamate derivative β-cyclodextrin bonded phase and a commercial (S)-(+)-1–(1-naphthyl) ethylcarbamate derivative β-cyclodextrin bonded phase on normal phase chromatographic condition. Results show that the prepared phenyl carbamate derivative β-cyclodextrin bonded phase has better enantiomeric selectivity to the series of compounds. A chiral recognition mechanism was suggested for the separation of these novel organic phosphorus enantiomers.     

Synthetic Studies on Sialoglycoconjugates 40: Stereocontrolled Synthesis of Sialyl Lewis X Epitope and Its Ceramide Derivative

Abstract

Stereocontrolled synthesis of sialyl Le^x epitope and its ceramide derivative with regard to the introduction of galactose or β-D-galactosyl ceramide into the terminal N-acetylglucosamine residue of sialyl Le^x determinant is described. Königs-Knorr condensation of 2-(trimethylsilyl)ethyl 2, 4, 6-tri-O-benzyl-β-D-galactopyranoside (4) with 3, 4, 6-tri-O-acetyl-2-deoxy-2-phthalimido-D-glucopyranosyl bromide (5) gave the desired β-glycoside 6, which was converted into 2-(trimethylsilyl)ethyl O-(2-acetamido-4, 6-O-benzylidene-2-deoxy-β-D-glucopyranosyl)-(l→3)-2, 4, 6-tri-O-benzyl-β-D-galactopyranoside (8) via removal of the phthaloyl and O-acetyl groups, followed by N-acetylation and 4, 6-O-benzylidenation. Glycosylation of 8 with methyl 2, 3, 4-tri-O-benzyl-1-thio-β-L-fucopyranoside (9) gave the α-glycoside (10), which was transformed by reductive ring-opening of the benzyliderie acetal into the acceptor (11). Dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling of 11 with methyl O-(methyl 5-acetamido-4, 7, 8, 9-tetra-O-acetyl-3, 5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-2, 4, 6-tri-O-benzoyl-l-thio-β-D-galactopyra-noside (12) afforded the desired pentasaccharide (13), which was converted into the α-trichloroacetimidate 16 via reductive removal of the benzyl groups, then O-acetylation, removal of the 2-(trimethyIsilyl)ethyl group and treatment with trichloroacetonitrile. Condensation of 16 with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-l, 3-diol (18) gave the β-glycoside 19, which was transformed into the title compound 21, via reduction of the azido group, coupling with octadecanoic acid, O-deacylation and hydrolysis of the methyl ester group. On the other hand, O-deacylation of 13 and subsequent hydrolysis of the methyl ester group gave the pentasaccharide epitope 17.     

Molecular Recognition and Cooperative Binding Ability of Fluorescent Dyes by Bridged Bisβ-cyclodextrin)s Tethered with Aromatic Diamine

A novel bridged bis(β-cyclodextrin),m-phenylenediimino-bridged bis(6-imino-6-deoxy-β-cyclodextrin) (2), was synthesized by the reaction of m-phenylenediamine and 6-deoxy-6-formyl-β-cyclodextrin. The inclusion complexation behavior of the novel bridged bis(β-cyclodextrin) 2,as well as native β-cyclodextrin (1),p-phenylenediamino-bridged bis(6-amino-6-deoxy-β-cyclodextrin) (3) and 4,4'-bianilino-bridged bis(6-amino-6-deoxy-β-cyclodextrin) (4) with representative fluorescent dye molecules, i.e., acridine red (AR), neutral red (NR), Rhodamine B (RhB), ammonium 8-anilino-1-naphthalenesulfonate (ANS) and sodium 6-toluidino-2-naphthalenesulfonate (TNS), was investigated at 25 °C in aqueous phosphate buffer solution (pH 7.20) by means of fluorescence, and circular dichroism, as well as 2D NMR spectrometry. The spectrofluorometric titrations have been performed to calculate the complex stability constants (K_S) and Gibbs free energy changes (Δ G°) for the stoichiometric 1 : 1 inclusion complexation of 1–4 with fluorescent dye molecules. The results obtained demonstrated that bis(β-cyclodextrin)s 2–4 showed much higher affinities toward these guest dyesthan native β-cyclodextrin 1. Typically, dimer 2 displayed the highest binding ability upon inclusion complexation with ANS, affording 35 times higher K_S value than native β-cyclodextrin. The significantlyenhanced binding abilities of these bis(β-cyclodextrin)s are discussed from thebinding mode and viewpoints of size/shape-fit concept and multiple recognition mechanism.     

Molecular Recognition of Aliphatic Alcohols and Carboxylic Acid by Chromophoric Cyclodextrins

Abstract

Molecular recognition behavior of eight cyclodextrin derivatives, i.e. mono(6-pyridinio-6-deoxy)-α-cyclodextrin (1α), mono(6-pyridinio-6-deoxy)-β-cyclodetrin (1β), mono(6-pyridinio-6-deoxy)-γ-cyclodextrin (1γ), mono[6-(p-picolinio)-6-deoxy]-β-cyclodextrin (2β), mono(6-anilino-6-deoxy)-β-cyclodextrin (3β), mono[6-(m-toluidino)-6-deoxy]-β-cyclodextrin (4β), mono[6-O-(8-quinolyl)]-β-cyclodextrin (5β), and novel mono[6-(2-naphthylamino)-6-deoxy]-β-cyclodextrin (6β), with a series of aliphatic alcohols and carboxylic acid has been investigated spectroscopically. Using the appended aromatic group as a spectral probe, spectroflurometric or spectropolarimetric titrations have been performed at 25°C in aqueous phosphate buffer solution (pH 7.20, 0.1 M) to determine the complex stability constants (K_s ) and Gibbs free energy changes (-δG°) for the stoichiometric 1:1 inclusion complexation of cyclodextrin derivatives with the guests. The results obtained demonstrate that the modified cyclodextrins are highly sensitive to the size/shape and hydrophobicity of guest molecules, and particularly 5β gives an excellent molecular selectivity up to 215 for 1-adamantanol/cyclohexanol. The binding ability and selectivity of the modified cyclodextrins (1α, 1β, and 1β-6β) are discussed from the view points of size/shape-fit concept, induced-fit interaction, and the multiple recognition mechanisms.     

Complex Formation of Hematoporphyrin with Cyclodextrins and 1,1′-Diheptyl-4,4′-bipyridinium Dibromide in Aqueous Solutions

At around 5×10^-6?mol?dm^-3 of hematoporphyrin (HP), an HP dimer exists as well as an HP monomer. The equilibrium constant for the dimerization of HP in pH 10.0 buffer has been evaluated to be 1.70×10⁵?mol^-1?dm³ from the HP concentration dependence of the absorption spectrum. In aqueous solution, HP forms 1:1 inclusion complexes with β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD). The fluorescence of HP is significantly enhanced by the addition of CDs. From simulations of the fluorescence intensity changes, the equilibrium constants for the formation of the CD–HP inclusion complexes have been estimated to be 200, 95.7, and 938?mol^-1?dm³ for β-CD, γ-CD, and TM-β-CD, respectively. HP forms a 1:1 complex with 1,1′-diheptyl-4,4′-bipyridinium dibromide (DHB) in aqueous solution. In contrast to the addition of CDs, the HP fluorescence is significantly quenched by the addition of DHB. The equilibrium constant for the formation of the HP–DHB complex has been evaluated to be 1.98×10⁵?mol^-1?dm³ from the fluorescence intensity change of HP. The addition of DHB to an HP solution containing β-CD induces a circular dichroism signal of negative sign, indicating the formation of a ternary inclusion complex involving β-CD, HP, and DHB. In contrast, there is no evidence for the formation of a ternary inclusion complex of HP with DHB and TM-β-CD.